The research proposed will determine whether the radioprotective drug, WR-2721, when given before the combinations of radiation and hypoxic cell sensitizers or radiation and alkylating agents will increase the effectiveness of radiotherapy. Due to pharmacokinetic differences between WR-2721 and the other two types of agents, WR-2721 selectively protects against radiation and the alkylating agents in the normal tissues, while leaving solid tumors to suffer the full effects of the treatment. For the same reasons it does not interfere with the ability of hypoxic cell sensitizers to sensitize the tumor. These studies will be conducted in tumor bearing mice and rats, with the objective being to determine relative effects in normal and tumor tissues under conditions which simulate the clinic. The combination of WR-2721, hypoxic cell sensitizers and radiation is solely concerned with local disease, while use of alkylating agents in this combination in place of hypoxic cell sensitizers expands this approach to include treatments of metastatic disease. In order to extend this approach to patients, we will also study the ability of human tissue samples, both normal and malignant, to absorb WR-2721 in vitro. If the results obtained are similar to those observed in experimental animals when assayed in vitro, a logical basis for proposing the clinical application of this approach will be available.